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Article: Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy

TitlePotent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy
Authors
Issue Date2015
Citation
Scientific Reports, 2015, v. 5, p. 11235 How to Cite?
Abstract© 2015, Nature Publishing Group. All rights reserved.Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel "cell-free" therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects.
Persistent Identifierhttp://hdl.handle.net/10722/216091
ISSN
2017 Impact Factor: 4.122
2015 SCImago Journal Rankings: 2.073
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorLiang, X-
dc.contributor.authorLiao, S-
dc.contributor.authorWang, W-
dc.contributor.authorWang, JJ-
dc.contributor.authorLI, X-
dc.contributor.authorDing, Y-
dc.contributor.authorLIANG, Y-
dc.contributor.authorGAO, F-
dc.contributor.authorYang, M-
dc.contributor.authorFu, Q-
dc.contributor.authorXu, A-
dc.contributor.authorChai, YH-
dc.contributor.authorHe, J-
dc.contributor.authorTse, HF-
dc.contributor.authorLian, Q-
dc.date.accessioned2015-08-21T13:53:57Z-
dc.date.available2015-08-21T13:53:57Z-
dc.date.issued2015-
dc.identifier.citationScientific Reports, 2015, v. 5, p. 11235-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10722/216091-
dc.description.abstract© 2015, Nature Publishing Group. All rights reserved.Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel "cell-free" therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects.-
dc.languageeng-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titlePotent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy-
dc.typeArticle-
dc.identifier.emailZhang, Y: zyl1999@hku.hk-
dc.identifier.emailLiao, S: lsy923@hkucc.hku.hk-
dc.identifier.emailWang, JJ: junwen@hku.hk-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.emailTse, HF: hftse@hkucc.hku.hk-
dc.identifier.emailLian, Q: qzlian@hkucc.hku.hk-
dc.identifier.authorityWang, JJ=rp00280-
dc.identifier.authorityXu, A=rp00485-
dc.identifier.authorityTse, HF=rp00428-
dc.identifier.authorityLian, Q=rp00267-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/srep11235-
dc.identifier.scopuseid_2-s2.0-84930959000-
dc.identifier.hkuros248330-
dc.identifier.hkuros263945-
dc.identifier.volume5-
dc.identifier.spage11235-
dc.identifier.epage11235-
dc.identifier.isiWOS:000209878800001-

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